Herpes simplex virus is a major cause of acute and recurrent viral diseases in man. The nervous system is a major target for infection by this virus and furthermore, serves as a reservoir for latent virus in sites such as the sensory ganglia. Immunologic defenses can influence the spread of virus to and within the nervous system. Mice inoculated in the footpad develop an ascending infection along neural channels of spread and provide an excellent model in which to study immunologic retardation of viral spread. Using this model, this proposal seeks to investigate immune defense mechanisms of relevance to the nervous system in two ways. The first is to study the ability of immune immunoglobulin (Ig) and subunits of immune Ig obtained from enzymatic digestion to restrict spread of virus from peripheral footpad sites in mice. The second portion of the proposal will be concerned with the basis of genetically transmitted resistance to infection seen in certain inbred strains of mice. Several aspects of the biologic expression of infection in these mice will be studied, including the ability of tissues to support viral replication, humoral and cell mediated immune function, and the ability to sustain latent infection of the dorsal root ganglion. These studies will further our understanding of the role of immune defenses in herpes simplex infection of the central nervous system.